Machine learning and biological validation identify sphingolipids as potential mediators of paclitaxel-induced neuropathy in cancer patients.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious therapy-limiting side effect of commonly used anticancer drugs. Previous studies suggest that lipids may play a role in CIPN. Therefore, the present study aimed to identify the particular types of lipids that are regulated as a consequence of paclitaxel administration and may be associated with the occurrence of post-therapeutic neuropathy.

The atypical sphingosine 1-phosphate variant, d16:1 S1P, mediates CTGF induction via S1P2 activation in renal cell carcinoma.

Sphingosine 1-phosphate (S1P) is a lipid mediator with numerous biological functions. The term 'S1P' mainly refers to the sphingolipid molecule with a long-chain sphingoid base of 18 carbon atoms, d18:1 S1P. The enzyme serine palmitoyltransferase catalyses the first step of the sphingolipid de novo synthesis using palmitoyl-CoA as the main substrate.

Beta adrenoceptor blockade ameliorates impaired glucose tolerance and alterations of the cerebral ceramide metabolism in an experimental model of ischemic stroke.

Background: Sphingolipids are versatile signaling molecules derived from membrane lipids of eukaryotic cells. Ceramides regulate cellular processes such as proliferation, differentiation and apoptosis and are involved in cellular stress responses. Experimental evidence suggests a pivotal role of sphingolipids in the pathogenesis of cardiovascular diseases, including ischemic stroke.

Low Serum Levels of (Dihydro-)Ceramides Reflect Liver Graft Dysfunction in a Real-World Cohort of Patients Post Liver Transplantation.

Patients after orthopic liver transplantation (OLT) are at risk of developing graft dysfunction. Sphingolipids (SL's) have been identified to play a pivotal role in the regulation of hepatocellular apoptosis, inflammation and immunity. We aimed to investigate the serum SL profile in a prospective real-world cohort of post-OLT patients.

Alteration of sphingolipid metabolism as a putative mechanism underlying LPS-induced BBB disruption.

Septic encephalopathy with confusion and agitation occurs early during sepsis and contributes to the severity of the disease. A decrease in the sphingosine-1-phosphate (S1P) blood levels has been shown in patients and in animal models of sepsis. The lipid mediator S1P is known to be involved in endothelial barrier function in a context-dependent manner.

Phosphorylation of murine SAMHD1 regulates its antiretroviral activity.

Background: Human SAMHD1 is a triphosphohydrolase that restricts the replication of retroviruses, retroelements and DNA viruses in noncycling cells. While modes of action have been extensively described for human SAMHD1, only little is known about the regulation of SAMHD1 in the mouse. Here, we characterize the antiviral activity of murine SAMHD1 with the help of knockout mice to shed light on the regulation and the mechanism of the SAMHD1 restriction and to validate the SAMHD1 knockout mouse model for the use in future infectivity studies.

S1P2/G12/13 Signaling Negatively Regulates Macrophage Activation and Indirectly Shapes the Atheroprotective B1-Cell Population.

Objectives: Monocyte/macrophage recruitment and activation at vascular predilection sites plays a central role in the pathogenesis of atherosclerosis. Heterotrimeric G proteins of the G12/13 family have been implicated in the control of migration and inflammatory gene expression, but their function in myeloid cells, especially during atherogenesis, is unknown.

Approach And Results: Mice with myeloid-specific deficiency for G12/13 show reduced atherosclerosis with a clear shift to anti-inflammatory gene expression in aortal macrophages.

Lack of effect of a P2Y6 receptor antagonist on neuropathic pain behavior in mice.

Accumulating evidence indicates that various subtypes of purinergic receptors (P2X and P2Y receptor families) play an essential role in the development and the maintenance of neuropathic pain. However, there is only limited data available about the role of P2Y6 receptors in pain processing. Here we detected P2Y6 receptor immunoreactivity in primary afferent neurons of mice and observed an upregulation in response to peripheral nerve injury.

Prostacyclin regulates spinal nociceptive processing through cyclic adenosine monophosphate-induced translocation of glutamate receptors.

Background: Prostacyclin (PGI2) is known to be an important mediator of peripheral pain sensation (nociception) whereas little is known about its role in central sensitization.

Methods: The levels of the stable PGI2-metabolite 6-keto-prostaglandin F1α (6-keto-PGF1α) and of prostaglandin E2 (PGE2) were measured in the dorsal horn with the use of mass spectrometry after peripheral inflammation. Expression of the prostanoid receptors was determined by immunohistology.

Analysis of sphingolipid and prostaglandin synthesis during zymosan-induced inflammation.

Sphingosine-1-phosphate (S1P) is generated through phosphorylation of sphingosine by two sphingosine kinases (SPHK-1 and -2). As extra- and intracellular messenger S1P fulfils multiple roles in inflammation such as mediating proinflammatory inputs or acting as chemoattractant. In addition, S1P induces cyclooxygenase-2 (COX-2) expression and the synthesis of proinflammatory prostanoids in several cell types.

PTGS-2-PTGER2/4 signaling pathway partially protects from diabetogenic toxicity of streptozotocin in mice.

Prostanoids are suggested to participate in diabetes pathology, but their roles are controversially discussed. The purpose of the current study was to examine the role of cyclooxygenase (prostaglandin synthase [PTGS]) enzymes and prostaglandin (PG) E(2) signaling pathways in streptozotocin (STZ)-induced type 1 diabetes. Blood glucose, insulin, and survival rate were studied in mice with targeted disruption of the genes for PTGS and PGE receptors (PTGERs).

Determination of basic drugs of abuse in human serum by online extraction and LC-MS/MS.

A new quantitation method for the determination of drugs of abuse (opiates, amphetamine and derivatives, cocaine, methadone and metabolites) in serum by using online extraction coupled to liquid chromatography (LC)-mass spectrometry (MS)/MS has been developed. The online extraction is carried out using two extraction columns simultaneously and one analytical column. One extraction column is loaded, while the other one is eluted by a gradient.